title: Tissue selective estrogen complex combinations with bazedoxifene/conjugated estrogens as a model.
abstract: The tissue selective estrogen complex (TSEC) pairs a selective estrogen receptor modulator (SERM) with one or more estrogens. Different TSECs are associated with distinct gene expression profiles in mammary gland and endometrial tissue according to the individual SERM and estrogen components. Few TSECs have been evaluated outside the laboratory. In preclinical trials, bazedoxifene (BZA) was distinct from other SERMs, with a neutral effect on mammary gland and endometrial tissue, and an antagonist effect on these tissues when combined with conjugated estrogens (CE). The only TSEC in an advanced stage of clinical development pairs BZA with CE. In large, randomized clinical trials, two doses, BZA 20 mg/CE 0.45 and 0.625 mg, reduced menopausal symptoms and prevented bone loss in postmenopausal women with a favorable safety profile on the breast, endometrium, and ovary, and with cardiovascular and venous thrombosis events similar to placebo. Improvements were seen in sleep, health-related quality of life, and treatment satisfaction. Compared with traditional, progestogen-containing hormone therapy, BZA/CE had higher rates of amenorrhea and reduced breast pain, with changes in breast density from baseline similar to placebo. Future TSECs identified in preclinical studies need to be tested in rigorous phase-3 clinical trials for effectiveness, safety and tolerability.
authors.affiliation: * Department of Obstetrics and Gynecology, Division of Midlife Health, University of Virginia Health System , Charlottesville, VA.
authors.forename: J V
authors.initials: JV
authors.lastname: Pinkerton
authors.forename: B S
authors.initials: BS
authors.lastname: Komm
authors.forename: S
authors.initials: S
authors.lastname: Mirkin
mesh_terms: D000818:Animals; D001284:Atrophy / Q000188:drug therapy; D004966:Estrogens, Conjugated (USP) / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D019584:Hot Flashes / Q000188:drug therapy*; D006801:Humans; D007211:Indoles / Q000494:pharmacology / Q000627:therapeutic use*; D050356:Lipid Metabolism / Q000187:drug effects; D015663:Osteoporosis, Postmenopausal / Q000517:prevention & control*; D011788:Quality of Life; D020845:Selective Estrogen Receptor Modulators / Q000494:pharmacology / Q000627:therapeutic use*; D012890:Sleep / Q000187:drug effects; D014621:Vagina / Q000473:pathology; D054556:Venous Thromboembolism / Q000139:chemically induced; D014844:Vulva / Q000473:pathology
chemical_list: D004966:Estrogens, Conjugated (USP); D007211:Indoles; D020845:Selective Estrogen Receptor Modulators; C447119:bazedoxifene